Research Projects

Dengue encephalitis is a serious illness contributing to 0.5-20% of all dengue cases. In India too, Dengue is the third leading cause of acute encephalitis syndrome causing considerable morbidity and mortality. Though there are known epidemiological and serological associations between dengue and acute encephalitis syndrome, there is little known about the dengue virus and the role of inflammatory processes in dengue associated AES. We would like to explore this association in this study. The objectives of our study would be to isolate dengue virus from children with acute encephalitis syndrome (AES) and characterize the virus strains in cell culture and animal models and to characterize the inflammatory milieu in AES cases with and without DENV and understanding the mechanism of blood-brain barrier disruption using in vitro 2D cultures. To achieve our objectives, the study will be conducted in 3 clinical sites and one laboratory site. There will be four types of participants recruited, all less than 15 years of age. The types of participants will be 40 AES patients with Dengue, 40 Dengue patients without AES, 20 AES patients without Dengue and 20 acute febrile illness (AFI) patients without dengue or AES. All children less than 15 years of age who present to any of the three centres and fit the definition of AES or AFI will be screened at admission into the ICU/ward by study personnel. Depending on the Dengue NS1 and IgM testing, the patients will be consecutively recruited to obtain the four categories of participants in required numbers across all the three sites. In addition to the routine blood samples and investigations done for the clinical management of the patients, all dengue positive participants will have a citrated (4 ml in a light blue top tube) and clotted (2ml in red top tube) blood collected at inclusion in the study. Subsequently, blood will be collected in clotted tube (2ml in red top tube) every alternate day up to a maximum of 3 samples and on the day of discharge. An additional blood sample will also be obtained on follow up 28 days (+/- 7 days) after the date of discharge. CSF samples, if available will also be sent for further analysis. The dengue isolates obtained from the dengue patients with and without AES will undergo whole genome sequencing and detailed molecular characterization. The differences in the viral characteristics between the dengue viruses causing AES and those that did not will be studied. In addition to this, the mediators of inflammation and the factors causing endothelial damage will also be studied between the different groups especially those with AES with and without dengue. This information can potentially provide the basic information required for developing interventions either in the form of directly acting anti-viral drugs or host directed therapy in AES cases due to dengue.